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Inhibition of vertebrate aldehyde oxidase as a therapeutic treatment for cancer, obesity, aging and amyotrophic lateral sclerosis

The aldehyde oxidases (AOXs) are a small sub-family of cytosolic molybdo-flavoenzymes, which are structurally conserved proteins and broadly distributed from plants to animals. AOXs play multiple roles in both physiological and pathological processes and AOX inhibition is of increasing significance in the development of novel drugs and therapeutic strategies. This review provides an overview of the evolution and the action mechanism of AOX and the role of each domain. The review provides an update of the polymorphisms in the human AOX. This review also summarises the physiology of AOX in different organs and its role in drug metabolism. The inhibition of AOX is a promising therapeutic treatment for cancer, obesity, aging and amyotrophic lateral sclerosis.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N351 – PubChem

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Visible Light Mediated Photoredox Catalytic Arylation Reactions

ConspectusIntroducing aryl- and heteroaryl moieties into molecular scaffolds are often key steps in the syntheses of natural products, drugs, or functional materials. A variety of cross-coupling methods have been well established, mainly using transition metal mediated reactions between prefunctionalized substrates and arenes or C-H arylations with functionalization in only one coupling partner. Although highly developed, one drawback of the established sp2-sp2 arylations is the required transition metal catalyst, often in combination with specific ligands and additives. Therefore, photoredox mediated arylation methods have been developed as alternative over the past decade.We begin our survey with visible light photo-Meerwein arylation reactions, which allow C-H arylation of heteroarenes, enones, alkenes, and alkynes with organic dyes, such as eosin Y, as the photocatalyst. A good number of examples from different groups illustrate the broad application of the reaction in synthetic transformations. While initially only photo-Meerwein arylation-elimination processes were reported, the reaction was later extended to photo-Meerwein arylation-addition reactions giving access to the photoinduced three component synthesis of amides and esters from alkenes, aryl diazonium salts, nitriles or formamides, respectively. Other substrates with redox-active leaving groups have been explored in photocatalyzed arylation reactions, such as diaryliodonium and triarylsulfonium salts, and arylsulfonyl chlorides. We discus some examples with their scope and limitations.The scope of arylation reagents for photoredox reactions was extended to aryl halides. The challenge here is the extremely negative reduction potential of aryl halides in the initial electron transfer step compared to, e.g., aryl diazonium or diaryliodonium salts. In order to reach reduction potentials over -2.0 V vs SCE two consecutive photoinduced electron transfer steps were used. The intermediary formed colored radical anion of the organic dye perylenediimide is excited by a second photon allowing the one electron reduction of acceptor substituted aryl chlorides. The radical anion of the aryl halide fragments under the loss of a halide ion and the aryl radical undergoes C-H arylation with biologically important pyrrole derivatives or adds to a double bond. Rhodamine 6G as an organic photocatalyst allows an even higher degree of control of the reaction. The dye is photoreduced in the presence of an amine donor under irradiation with green light (e.g., 530 nm), yielding its radical anion, which is a mild reducing reagent. The hypsochromic shift of the absorption of the rhodamine 6G radical anion toward blue region of the visible light spectrum allows its selective excitation using blue light (e.g., 455 nm). The excited radical anion is highly reducing and able to activate even bromoanisole for C-H arylation reactions, although only in moderate yield.Photoredox catalytic C-H arylation reactions are valuable alternatives to metal catalyzed reactions. They have an excellent functional group tolerance, could potentially avoid metal containing catalysts, and use visible light as a traceless reagent for the activation of arylating reagents.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N164 – PubChem

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Copper-Mediated Oxidative Functionalization of C(sp3)-H Bonds with Isoquinolines: Two-Step Synthesis of 5-Oxaprotoberberinones

A copper-mediated oxidative functionalization of C(sp3)-H bonds with isoquinolines via a radical process without ligands was achieved. The present system exhibits a novel pathway for the preparation of N-alkyl (benzyl) isoquinolin-1(2H)-ones in moderate to high yields. In addition, this procedure provides a simple method to afford 5-oxaprotoberberinones and their derivatives in two steps.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N469 – PubChem

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Trends and progress in the characterization of stationary phases for reversed-phase liquid chromatography

The state-of-the-art and progress in the characterization of reversed-phase liquid chromatographic (RPLC) columns are discussed. Existing column tests are compared with tests under development. The validity of several test parameters, e.g. hydrophobicity and silanol activity, is also discussed. Solvent and eluent properties are treated with respect to retention and selectivity. Developments to improve the chemical stability of RPLC phases and thus column lifetime are reviewed. It is shown that substantial progress has been made in the manufacturing of RPLC columns, enabling their use over a wide variety of experimental conditions. In addition, general measures to significantly extend their lifespan are discussed. The substantial improvements in batch-to-batch and column-to-column repeatabilities achieved during the last two decades are also reviewed.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N113 – PubChem

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An air-stable bisboron complex: A practical bidentate Lewis acid catalyst

We report an air-stable bisboron complex as an efficient catalyst for the inverse electron-demand Diels-Alder (IEDDA) reaction of 1, 2-diazine as well as 1, 2, 4, 5-tetrazine. Its stability towards air and moisture was demonstrated by NMR studies enabling its application in organic transformations without glovebox. A one-pot procedure for its synthesis was developed starting from 1, 2-bis(trimethylsilyl) benzene greatly enhancing its practicality. Comparative reactions were carried out to evaluate its catalytic activity in IEDDA reactions of diazine including phthalazine as well as 1, 2, 4, 5-tetrazine.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N187 – PubChem

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Applications of tandem Diels?Alder/sigmatropic rearrangement reactions to natural product synthesis

In this non-comprehensive review a selection of tandem processes combining sigmatropic rearrangement with Diels?Alder reactions is presented. The synthetic utility of these two transformations is indisputable as they can lead to complex natural products in an efficient and selective way. Most of the examples presented here have been chosen in view of their application to natural products synthesis. The emphasis of the discussion is put on the illustration of new strategic disconnections becoming accessible thanks to tandem processes

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Phthalazine – Wikipedia,
Phthalazine | C8H6N317 – PubChem

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Recent advances in the preparation and application of organic? inorganic hybrid magnetic nanocatalysts on multicomponent reactions

The combination of advantages of multicomponent reactions (MCRs) and magnetic nano catalysts is going to be an emerging and strategic area and is an ideal blend for the development of sustainable methodologies in organic synthesis in green and benign media. This review focuses on the synthesis, functionalization, and application of organic-inorganic hybrid magnetic nanoparticles as novel task-specific catalysts on multicomponent reactions (MCRs) in recent years. So, properly magnetic nanoparticles can be used as building blocks for the fabrication of various functional moieties, and their application in catalysis of MCRs will be briefly reviewed. The heterogenization of the catalyst using magnetic nanoparticles allows it to be recovered and reused using an external magnet. The approach to magnetic separation is not only easy, cost-effective, favorable for work-up procedures and industrial applications, but also is usually more effective than filtration or centrifugation as it diminishes the loss of the catalyst.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N77 – PubChem

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Chemiluminescence properties of luminol related o-hydroxybenzimidazole analogues: Experimental and DFT based approach to photophysical properties

Novel luminol-isoluminol derivatives containing o-hydroxyphenyl benzimidazole unit were synthesized from aromatic aldehydes and diaminophthalates followed by heating under reflux with hydrazine hydrate. The chemiluminescent properties were studied in hydrogen peroxide, potassium hexacyanoferrate(III) and sodium hydroxide solution. The chemiluminescence properties were compared with the standard luminol and isoluminol systems it was observed that the chemiluminescence properties of the novel derivatives were superior to luminol and isoluminol. Density Functional Theory computations have been used in order to have a greater understanding of the structural, molecular, electronic and photophysical properties. The experimental absorption and emission wavelength values were in good agreement with the computed vertical excitation and emission values.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N122 – PubChem

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Synthesis of new analogs of 3-methyl-[1,2,4] triazolo [3,4-a] phthalazines via Suzuki coupling and evaluation of their anticancer and antimicrobial activity

A series of new N-aryl substituted phenyl acetamide analogs of 3-methyl-[1,2,4] triazolo[3,4-a] phthalazines were synthesized starting from commercially available, in-expensive phthalic anhydride in good yields (65-75 %) via Suzuki Coupling. These compounds were tested for inhibition activity against HCT 116 cancer cell line by using MIT assay. Among the library of compounds, N-(3-methoxyphenyl)-2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl) acetamide followed by 2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl)-N-(m-tolyl) acetamide and N-(3-chlorophenyl)-2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl) acetamide were found to be active compounds with IC50 of 70 to and 90 mug mL-1. Further, the compounds were also screened for their antimicrobial activities.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N244 – PubChem

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Visible-light-mediated Minisci C-H alkylation of heteroarenes with unactivated alkyl halides using O2 as an oxidant

Herein, we report a protocol for direct visible-light-mediated Minisci C-H alkylation of heteroarenes with unactivated alkyl halides using molecular oxygen as an oxidant at room temperature. This mild protocol is compatible with a wide array of sensitive functional groups and has a broad substrate scope. Notably, functionalization of (iso)quinolines, pyridines, phenanthrolines, quinazoline, and other heterocyclic compounds with unactivated primary, secondary, and tertiary alkyl halides proceeds smoothly under the standard conditions. The robustness of this protocol is further demonstrated by the late-stage functionalization of complex nitrogen-containing natural products and drugs.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N128 – PubChem